Digital Commons Network^™

Structure-Activity Relationships Of A–And B-Type Proanthocyanidins In Long-Term Dentin Biomodification And Biocompatibility, Yvette Alania, Mariana Reis-Havlat, Shu-Xi Jing, Fahimeh Tabatabaei, James B. Mcalpine, Shao-Nong Chen, Guido F. Pauli, Ana K. Bedran-Russo

School of Dentistry Faculty Research and Publications

Objective

To explore the structure-activity relationships of plant-based proanthocyanidins (PACs) with dental pulp stem cells (DPSCs) and the long-term biomechanical stability of PAC-modified dentin extracellular matrix (ECM).

Methods

Mid-coronal dentin ECM (n= 8) was treated with eight PAC tetramers and trimers with varying A-/B-type linkages. Chemo-mechanical analyses included dynamic mechanical analysis and ATR-FTIR spectroscopy. Viscoelastic components were calculated after PAC biomodification, 18-month incubation, and protein destabilization. Collagen structure was assessed via IR amide absorbance ratios. DPSCs were cultured with PACs at different concentrations (100, 10, and 1 μg/mL) to measure proliferation. ANOVA and post-hoc tests were used for …

Identification Of Diverse Bacteriophages Associated With Bees And Hoverflies, Rohan A. Bandoo, Simona Kraberger, Cahit Ozturk, Michael C. Lund, Qiyun Zhu, Chelsea N. Cook, Brian Smith, Arvind Varsani

Biological Sciences Faculty Research and Publications

Bacteriophages are the most numerous, ubiquitous, and diverse biological entities on the planet. Prior studies have identified bacteriophages associated with pathogenic and commensal microbiota of honeybees. In this study we expand on what is known about bacteriophages from the lineages Caudoviricetes, Inoviridae, and Microviridae, which are associated with honeybees (Apidae, Apis mellifera), solitary bees of the genus Nomia (Halictidae, Nomia), and hoverflies (Syrphidae). The complete genomes of seven caudoviruses, seven inoviruses, and 288 microviruses were assembled from honeybees (n = 286) and hoverflies in Arizona (n = 2). We used bacterial host predictive …

Schizachyrium Scoparium (C4) Better Tolerates Drought Than Andropogon Gerardii (C4) Via Constant Co2 Supply For Photosynthesis During Water Stress, Alina Dekirmenjian, Diego Montano, Michelle L. Budny, Nathan P. Lemoine

Biological Sciences Faculty Research and Publications

Climate change is dramatically altering global precipitation patterns across terrestrial ecosystems, making it critically important that we understand both how and why plant species vary in their drought sensitivities. Andropogon gerardii and Schizachyrium scoparium, both C₄ grasses, provide a model system for understanding the physiological mechanisms that determine how species of a single functional type can differ in drought responses, an issue remains a critical gap in our ability to model and predict the impacts of drought on grassland ecosystems. Despite its greater lability of foliar water content, previous experiments have demonstrated that S. scoparium maintains higher photosynthetic …

Bacillus Subtilis-Derived Peptides Disrupt Quorum Sensing And Biofilm Assembly In Multidrug-Resistant Staphylococcus Aureus, Kyle R. Leistikow, Daniel S. May, Won Se Suh, Gabriel Vargas Asensio, Adam J. Schaenzer, Cameron R. Currie, Krassimira R. Hristova

Biological Sciences Faculty Research and Publications

Multidrug-resistant Staphylococcus aureus is one of the most clinically important pathogens in the world, with infections leading to high rates of morbidity and mortality in both humans and animals. The ability of S. aureus to form biofilms protects cells from antibiotics and promotes the transfer of antibiotic resistance genes; therefore, new strategies aimed at inhibiting biofilm growth are urgently needed. Probiotic species, including Bacillus subtilis, are gaining interest as potential therapies against S. aureus for their ability to reduce S. aureus colonization and virulence. Here, we search for strains and microbially derived compounds with strong antibiofilm activity against multidrug-resistant S. …

Developmental Patterns Underlying Variation In Form And Function Exhibited By House Gecko Toe Pads, Aaron H. Griffing, Tony Gamble, Ashmika Behere, Timothy E. Higham, Greta M. Keller, John Resener, Thomas J. Sanger

Biological Sciences Faculty Research and Publications

Adhesive toe pads have evolved numerous times over lizard evolutionary history, most notably in geckos. Despite significant variation in adult toe pad morphology across independent origins of toe pads, early developmental patterns of toe pad morphogenesis are similar among distantly related species. In these distant phylogenetic comparisons, toe pad variation is achieved during the later stages of development. We aimed to understand how toe pad variation is generated among species sharing a single evolutionary origin of toe pads (house geckos—Hemidactylus). We investigated toe pad functional variation and developmental patterns in three species of Hemidactylus, ranging from highly …

Properties And Behavior Of Tricarbonyl Manganese Scorpionate Complexes, Billy Shone

Master's Theses (2009 -)

Manganese tricarbonyl complexes have widely been studied for their ability to release carbon monoxide (CO) in the presence of light for potential applications in cancer therapy and in catalysis. Most studies focus on the kinetics and quantity of CO release and the overall impact on cell death. Far fewer studies identify the manganese intermediates and final products after decarbonylation. Identification of such products would be critical to improving reactivity and understanding potential (undesirable) side effects in future applications employing these CO releasing molecules (CORMs). Recently, nitrogen confused C-scorpionate ligands were introduced by the Gardinier group where a pyrazolyl ring is …

Spatial Sequestration Of Misfolded Proteins In Neurodegenerative Diseases, Sarah Rolli, Emily M. Sontag

Biological Sciences Faculty Research and Publications

Properly folded, functional proteins are essential for cell health. Cells sustain protein homeostasis, or proteostasis, via protein quality control (PQC) mechanisms. It is currently hypothesized that a breakdown in proteostasis during ageing leads to the accumulation of protein aggregates in the cell and disease. Sequestration of misfolded proteins into PQC compartments represents one branch of the PQC network. In neurodegenerative diseases, certain proteins form abnormal protein deposits. Which PQC compartments house misfolded proteins associated with neurodegenerative diseases is still being investigated. It remains unclear if sequestration of these misfolded proteins is toxic or protective to the cell. Here, we review …

Sex-Specific Aging In Animals: Perspective And Future Directions, Anne M. Bronikowski, Richard P. Meisel, Peggy R. Biga, James R. Walters, Judith E. Mank, Erica Larschan, Gerald S. Wilkinson, Nicole Valenzuela, Ashley Mae Conard, João Pedro De Magalhães, Jingyue (Ellie) Duan, Amy E. Elias, Tony Gamble, Rita M. Graze, Kristin E. Gribble, Jill A. Kreiling, Nicole C. Riddle

Biological Sciences Faculty Research and Publications

Sex differences in aging occur in many animal species, and they include sex differences in lifespan, in the onset and progression of age-associated decline, and in physiological and molecular markers of aging. Sex differences in aging vary greatly across the animal kingdom. For example, there are species with longer-lived females, species where males live longer, and species lacking sex differences in lifespan. The underlying causes of sex differences in aging remain mostly unknown. Currently, we do not understand the molecular drivers of sex differences in aging, or whether they are related to the accepted hallmarks or pillars of aging or …

A Cluster Analytic Approach To Examining The Role Of Cortisol In The Development Of Post-Traumatic Stress And Dysphoria In Adult Traumatic Injury Survivors, Devi Jayan, Terri A Deroon-Cassini, Garrett Sauber, Cecilia J. Hillard, Jacklynn M. Fitzgerald

Psychology Faculty Research and Publications

Identification of specific risk factors for posttraumatic stress disorder (PTSD) versus depression after trauma has been challenging, in part due to the high comorbidity of these disorders. As exposure to trauma triggers activation of the hypothalamic-pituitary-adrenal (HPA)-axis, examining atypical stress responses via HPA-axis hormones, namely cortisol, may help in the delineation of these disorders. Indeed, extant research demonstrates that, following stress, individuals with chronic PTSD exhibit hypocortisolism (e.g., lower cortisol response than controls), while those with chronic depression exhibit hypercortisolism (e.g., higher response than controls). Less is known about the role of cortisol and these seemingly disparate profiles immediately following …

Local Canopy Disturbance As An Explanation For Long-Term Increases In Liana Abundance, Stefan A. Schnitzer, David M. Defilippis, Marco Visser, Sergio Estrada-Villegas, Rigoberto Rivera-Camaña, Boris Bernal, Salomé Peréz, Abelino Valdéz, Seberino Valdéz, Antonio Aguilar, James W. Dalling, Eben N. Broadbent, Angelica M. Almeyda Zambrano, Stephen P. Hubbell, Maria Garcia-Leon

Biological Sciences Faculty Research and Publications

Canopy disturbance explains liana abundance and distribution within tropical forests and thus may also explain the widespread pattern of increasing liana abundance; however, this hypothesis remains untested. We used a 10-year study (2007–2017) of 117,100 rooted lianas in an old-growth Panamanian forest to test whether local canopy disturbance explains increasing liana abundance. We found that liana density increased 29.2% and basal area 12.5%. The vast majority of these increases were associated with clonal stem proliferation following canopy disturbance, particularly in liana-dense, low-canopy gaps, which had far greater liana increases than did undisturbed forest. Lianas may be ecological niche constructors, arresting …

Temperature Stressed Caenorhabditis Elegans Males Fail To Mate Successfully And Successful Males Produce Very Few Viable Cross Progeny, Nicholas B. Sepulveda, Lisa N. Petrella

Biological Sciences Faculty Research and Publications

Exposure to moderate temperature stress can have profoundly negative effects on an organism’s reproductive capacity at temperatures where there are minimal or indiscernible effects on the organism as a whole. These negative effects are often more pronounced in males of the species that produce sperm. Previously we showed that few males of Caenorhabditis elegans wild type strains are able to successfully produce any cross progeny after experiencing temperature stress. However, these experiments did not assess the number of progeny from temperature stressed males. To understand if temperature stress can reduce the number of progeny a male sires, we crossed temperature …

A Chromosome-Level Genome Assembly Of The Parasitoid Wasp, Cotesia Glomerata (Hymenoptera: Braconidae), Brendan J. Pinto, Jerome J. Weis, Tony Gamble, Paul J. Ode, Ryan Paul, Jennifer M. Zaspel

Biological Sciences Faculty Research and Publications

Hymenopterans make up about 20% of all animal species, but most are poorly known and lack high-quality genomic resources. One group of important, yet understudied hymenopterans are parasitoid wasps in the family Braconidae. Among this understudied group is the genus Cotesia, a clade of ~1,000 species routinely used in studies of physiology, ecology, biological control, and genetics. However, our ability to understand these organisms has been hindered by a lack of genomic resources. We helped bridge this gap by generating a high-quality genome assembly for the parasitoid wasp, Cotesia glomerata (Braconidae; Microgastrinae). We generated this assembly using multiple sequencing …

Acute White Matter Integrity Post-Trauma And Prospective Posttraumatic Stress Disorder Symptoms, Carissa N. Weis, Ashley A. Huggins, Tara A. Miskovich, Jacklynn M. Fitzgerald, Kenneth P. Bennett, Jessica L. Krukowski, E. Kate Webb, Terri A Deroon-Cassini, Christine L. Larson

Psychology Faculty Research and Publications

Background: Little is known about what distinguishes those who are resilient after trauma from those at risk for developing posttraumatic stress disorder (PTSD). Previous work indicates white matter integrity may be a useful biomarker in predicting PTSD. Research has shown changes in the integrity of three white matter tracts—the cingulum bundle, corpus callosum (CC), and uncinate fasciculus (UNC)—in the aftermath of trauma relate to PTSD symptoms. However, few have examined the predictive utility of white matter integrity in the acute aftermath of trauma to predict prospective PTSD symptom severity in a mixed traumatic injury sample.

Method: Thus, the current study …

Microbial Find, Inform, And Test Model For Identifying Spatially Distributed Contamination Sources: Framework Foundation And Demonstration Of Ruminant Bacteroides Abundance In River Sediments, Corinne Wiesner-Friedman, Rachelle E. Beattie, Jill R. Stewart, Krassimira R. Hristova, Marc L. Serre

Biological Sciences Faculty Research and Publications

Microbial pollution in rivers poses known ecological and health risks, yet causal and mechanistic linkages to sources remain difficult to establish. Host-associated microbial source tracking (MST) markers help to assess the microbial risks by linking hosts to contamination but do not identify the source locations. Land-use regression (LUR) models have been used to screen the source locations using spatial predictors but could be improved by characterizing transport (i.e., hauling, decay overland, and downstream). We introduce the microbial Find, Inform, and Test (FIT) framework, which expands previous LUR approaches and develops novel spatial predictor models to characterize the transported contributions. We …

Design And Synthesis Of Selective Estrogen Receptor Agonists, Edward Edward Wetzel

Dissertations (1934 -)

Estrogens are hormones that regulates many different physiological functions. A decline in estrogen leads to significant issues that decrease the quality of life. Past treatments of menopausal symptoms included the administration of estrogen. However, side effects such as an increased risk of breast cancer, made this an unattractive therapeutic option. When a new estrogen receptor (ERβ) was discovered, it provided new hope for hormone replacement therapy (HRT). ERβ was shown to inhibit tumor growth, whereas ERα regulates breast cancer proliferation in certain types of breast cancer. The therapeutic benefits of targeting ERβ are vast; herein we focus on the benefits …

The Role Of System Xc- In Cognition: The Importance Of Neuron-Astrocyte Signaling, Evan Michael Hess

Dissertations (1934 -)

The biological basis of human intelligence is largely a mystery, but likely required evolutionary adaptations to achieve the information processing capacity needed to expand the complexity of cognition among species. The link between evolutionary expansion of signaling complexity in the brain and cognition has largely focused on neuronal mechanisms, in part because information processing has historically been attributed to these cells. However, astrocytes are emerging as a second type of brain cell that is capable of processing information due to their capacity to release glutamate and, thereby, regulate neural circuits. Hence, a modern question is whether astrocytes contributed to the …

1. Dft-Guided Discovery Of Hybrid Catalysts For C-C Bond Formation; 2. Synthesis Of A Reported Pdi Inhibitor, Eric Greve

Dissertations (1934 -)

1. Dual amine/pi Lewis acid catalyst systems have been reported for intramolecular direct additions of aldehydes/ketones to unactivated alkynes and occasionally alkenes, but related intermolecular reactions are rare. We reasoned that bulky metal ligands and bulky amine catalysts could minimize catalyst poisoning and could facilitate certain examples of direct intermolecular additions of unactivated aldehydes/ketones to alkenes/alkynes. Density Functional Theory (DFT) ground state calculations on putative catalytic intermediates for alkyne versus organocatalyst complexation to the -acid, and also the key carbon-carbon bond formation were used to prioritize ligand/organocatalyst combinations. Our calculations suggested that PyBOX-Pt(II) catalysts for alkene/alkyne activation could be combined …

The Weibull Topp-Leone Generated Family Of Distributions: Statistical Properties And Applications, Hamid Karamikabir, Mahmoud Afshari, Haitham M. Yousof, Morad Alizadeh, Gholamhossein G. Hamedani

Mathematical and Statistical Science Faculty Research and Publications

Statistical distributions are very useful in describing and predicting real world phenomena. Consequently, the choice of the most suitable statistical distribution for modeling given data is very important. In this paper, we propose a new class of lifetime distributions called the Weibull Topp-Leone Generated (WTLG) family. The proposed family is constructed via compounding the Weibull and the Topp-Leone distributions. It can provide better fits and is very flexible in comparison with the various known lifetime distributions. Several general statistical properties of the WTLG family are studied in details including density and hazard shapes, limit behavior, mixture representation, skewness and kurtosis, …

The Poisson Topp Leone Generator Of Distributions For Lifetime Data: Theory, Characterizations And Applications, Faton Merovci, Haitham M. Yousof, Gholamhossein Hamedani

Mathematical and Statistical Science Faculty Research and Publications

We study a new family of distributions defined by the minimum of the Poisson random number of independent identically distributed random variables having a Topp Leone-G distribution (see Rezaei et al., (2016)). Some mathematical properties of the new family including ordinary and incomplete moments, quantile and generating functions, mean deviations, order statistics, reliability and entropies are derived. Maximum likelihood estimation of the model parameters is investigated. Some special models of the new family are discussed. An application is carried out on real data set applications sets to show the potentiality of the proposed family.

The Marshall-Olkin Exponentiated Generalized G Family Of Distributions: Properties, Applications, And Characterizations, Haitham M. Yousof, Mahdi Rasekhi, Morad Alizadeh, Gholamhossein Hamedani

Mathematical and Statistical Science Faculty Research and Publications

In this paper, we propose and study a new class of continuous distributions called the Marshall-Olkin exponentiated generalized G (MOEG-G) family which extends the Marshall-Olkin-G family introduced by Marshall and Olkin [A. W. Marshall, I. Olkin, Biometrika 84 (1997), 641-652]. Some of its mathematical properties including explicit expressions for the ordinary and incomplete moments, generating function, order statistics and probability weighted moments are derived. Some characteristics of the new family are presented. Maximum likelihood estimation for the model parameters under uncensored and censored data is addressed in Section 5 as well as a simulation study to assess the performance of …

Route Exploration And Synthesis Of The Reported Pyridone-Based Pdi Inhibitor Stk076545, Eric Greve, Sergey V. Lindeman, Christina Scartelli, Lin Lin, Robert Flaumenhaft, Chris Dockendorff

Chemistry Faculty Research and Publications

The enzyme protein disulfide isomerase (PDI) is essential for the correct folding of proteins and the activation of certain cell surface receptors, and is a promising target for the treatment of cancer and thrombotic conditions. A previous high-throughput screen identified the commercial compound STK076545 as a promising PDI inhibitor. To confirm its activity and support further biological studies, a resynthesis was pursued of the reported β-keto-amide with an N-alkylated pyridone at the α-position. Numerous conventional approaches were complicated by undesired fragmentations or rearrangements. However, a successful 5-step synthetic route was achieved using an aldol reaction with an α-pyridone allyl …

Localized Dielectric Loss Heating In Dielectrophoresis Devices, Tae Joon Kwak, Imtiaz Hossen, Rashid Bashir, Woo-Jin Chang, Chung-Hoon Lee

Electrical and Computer Engineering Faculty Research and Publications

Temperature increases during dielectrophoresis (DEP) can affect the response of biological entities, and ignoring the effect can result in misleading analysis. The heating mechanism of a DEP device is typically considered to be the result of Joule heating and is overlooked without an appropriate analysis. Our experiment and analysis indicate that the heating mechanism is due to the dielectric loss (Debye relaxation). A temperature increase between interdigitated electrodes (IDEs) has been measured with an integrated micro temperature sensor between IDEs to be as high as 70 °C at 1.5 MHz with a 30 V_pp applied voltage to our ultra-low …

The Transcriptome Of The Veiled Chameleon (Chamaeleo Calyptratus): A Resource For Studying The Evolution And Development Of Vertebrates, Brendan John Pinto, Daren C. Card, Todd A. Castoe, Raul E. Diaz Jr., Stuart V. Nielsen, Paul A. Trainor, Tony Gamble

Biological Sciences Faculty Research and Publications

Purpose

The veiled chameleon (Chamaeleo calyptratus) is an emerging model system for studying functional morphology and evolutionary developmental biology (evo‐devo). Chameleons possess body plans that are highly adapted to an arboreal life style, featuring laterally compressed bodies, split hands/ft for grasping, a projectile tongue, turreted independently moving eyes, and a prehensile tail. Despite being one of the most phenotypically divergent clades of tetrapods, genomic resources for chameleons are severely lacking.

Methods

To address this lack of resources, we used RNAseq to generate 288 million raw Illumina sequence reads from four adult tissues (male and female eyes and gonads) …

The Alpha-Activator Complex, Cellular Maturation, And Catalytic Mechanism Of Iron-Type Nitrile Hydratase, Wasantha Lankathilaka Karunagala Pathiranage

Dissertations (1934 -)

In industry, chemicals are typically synthesized through catalytically accelerated chemical processes. The use of biocatalysts is an increasingly important trend in achieving environmentally friendly chemical production processes. Nitrile Hydratases (NHases) are well-known biocatalysts that are used by several manufacturers such as Mitsubishi Rayon Corporation and Lonza for the conversion of acrylonitrile to acrylamide and 3-cyanopyridine to nicotinamide, respectively. Amides, in general, are used in polymer preparation, adhesive manufacturing, and the paper industry. Refrigeration is needed in the enzymatic hydration process on the industrial scale to maintain a low reaction temperature to stabilize the NHase enzyme. The use of whole cells …

Distinct Proteostasis Circuits Cooperate In Nuclear And Cytoplasmic Protein Quality Control, Rahul S. Samant, Christine M. Livingston, Emily M. Sontag, Judith Frydman

Biological Sciences Faculty Research and Publications

Protein misfolding is linked to a wide array of human disorders, including Alzheimer’s disease, Parkinson’s disease and type II diabetes^1,2. Protective cellular protein quality control (PQC) mechanisms have evolved to selectively recognize misfolded proteins and limit their toxic effects^{3,4,5,6,7,8,9}, thus contributing to the maintenance of the proteome (proteostasis). Here we examine how molecular chaperones and the ubiquitin–proteasome system cooperate to recognize and promote the clearance of soluble misfolded proteins. Using a panel of PQC substrates with distinct characteristics and localizations, we define distinct chaperone and ubiquitination circuitries that execute quality control in the cytoplasm and nucleus. …

Empirical Bayesian Approach To Testing Multiple Hypotheses With Separate Priors For Left And Right Alternatives, Naveen K. Bansal, Mehdi Maadooliat, Steven J. Schrodi

Mathematics, Statistics and Computer Science Faculty Research and Publications

We consider a multiple hypotheses problem with directional alternatives in a decision theoretic framework. We obtain an empirical Bayes rule subject to a constraint on mixed directional false discovery rate (mdFDR≤α) under the semiparametric setting where the distribution of the test statistic is parametric, but the prior distribution is nonparametric. We proposed separate priors for the left tail and right tail alternatives as it may be required for many applications. The proposed Bayes rule is compared through simulation against rules proposed by Benjamini and Yekutieli and Efron. We illustrate the proposed methodology for two sets of …

Photochemical Expulsion Of Leaving Groups From A Naphthothiophene-2-Carboxamide Linked To A Chromophore, Lingzi Li

Dissertations (1934 -)

Two bichromophoric systems were synthesized which have thioxanthone as the chromophore that absorbs the incident light and a naphthothiophene-2-carboxanilide, which serves as a triplet excited state energy acceptor. Upon excitation the triplet excited state of the thioxanthone is populated via intersystem crossing, which is efficient with isc = 0.68. Based on the relative energies of the triplet excited states of thioxanthone (ET = 65 kcal mol-1) and naphthothiophene (ET = 51 kcal mol-1), the subsequent triplet excited state energy transfer to generate the triplet excited state of the naphthothiophene-2-carboxamide should be a very rapid process that is 14 kcal mol1 …

Photoremovable Protecting Groups Based On Electrocyclization With Leaving Group Expulsion Via A Proposed Zwitterion, Gilbert Ndzeidze

Dissertations (1934 -)

The triplet excited state of thioxanthone produced by photolysis undergoes reversible triplet energy transfer with a trimethylene - linked benzothiophene-2-carboxanilide ring system. The ensuing electrocyclic ring closure of the anilide moiety produces a putative zwitterionic intermediate that is capable of expelling leaving groups (LG-) from the C-3 position of the benzothiophene ring. Stern-Volmer quenching studies with cyclohexadiene as quencher furnish the rate constants for the triplet excitation transfer in the forward and reverse directions, which can be expressed as an equilibrium constant K = 0.058. Overall, the rate of triplet excited state reaction becomes K x kr = 5.7 x …

Type I General Exponential Class Of Distributions, Gholamhossein G. Hamedani, Haitham M. Yousof, Mahdi Rasekhi, Morad Alizadeh, Seyed Morteza Najibi

Mathematics, Statistics and Computer Science Faculty Research and Publications

We introduce a new family of continuous distributions and study the mathematical properties of the new family. Some useful characterizations based on the ratio of two truncated moments and hazard function are also presented. We estimate the model parameters by the maximum likelihood method and assess its performance based on biases and mean squared errors in a simulation study framework.

Design And Synthesis Of Selective Estrogen Receptor Β Agonists And Their Pharmacology, K. L. Iresha Sampathi Perera

Dissertations (1934 -)

Estrogens (17β-estradiol, E2) have garnered considerable attention in influencing cognitive process in relation to phases of the menstrual cycle, aging and menopausal symptoms. However, hormone replacement therapy can have deleterious effects leading to breast and endometrial cancer, predominantly mediated by estrogen receptor-alpha (ERα) the major isoform present in the mammary gland and uterus. Further evidence supports a dominant role of estrogen receptor-beta (ERβ) for improved cognitive effects such as enhanced hippocampal signaling and memory consolidation via estrogen activated signaling cascades. Creation of the ERβ selective ligands is challenging due to high structural similarity of both receptors. Thus far, several ERβ …